Metalated Nitriles: Unmasking Fundamental Reactivity

该项目由化学部化学合成计划资助，研究小组正在探索腈的全新反应。该提案在几个领域产生了影响；提升丁腈化学，培养和发展学生，提高学生的写作能力。这项研究分为三个大领域，将开发新的腈反应，用于合成与药物、农用化学品和新材料合成相关的环碳基支架。该提案的前三分之一侧重于极快地合成双环腈，中间三分之一开发了创建新碳-碳键的反直觉方法，提案的最后一部分开发了反应性腈中间体的新途径，以控制腈取代支架的三维形状。该项目在培养学生和博士后助理，特别是少数族裔和女性方面继续保持着良好的记录，为科学事业提供了一批聪明、上进心强的学生。该方法的特点是大力开展研究培训，对本科生和研究生进行协同指导，并通过团体教育活动和年度专业发展务静会强调职业生活的平衡。通过复习写作策略来提高写作技巧，使本科生和研究生从初学者过渡到专家实践者。该方法同时解决了许多学生普遍的写作缺陷，同时灌输了批判性评估主要文献的工具。将该策略发表在《化学教育杂志》上，可以让其他人在其他学生身上复制该策略。技术摘要：本项目专注于融合概念上的新键结构和新化学实体，其中许多挑战传统工艺。初步结果表明，单步合成手性癸酮是可行的，有可能取代基于wieland - micescher酮的多步合成技术。一种极不寻常的平衡正在形成中，它改变了四元桥头堡中心的立体化学性质；挑战传统观念的过程。金属化腈与未活化烯烃的反直觉烷基化反应是快速组装三环酮。一种互补的烯烃加成使用s -酮亚胺作为特别有吸引力的亲核试剂来解决两个长期存在的挑战：快速获得稳定的酮亚胺亲核试剂和腈基烯化。提案的最后一部分提供了一个正交的，创新的不对称烷基化与金属化腈。总的来说，拟议的研究利用了腈的独特反应性，其长期目标是将金属化腈烷基化提高到与烯醇酯烷基化相当的影响水平。

Non-technical AbstractIn this project, funded by the Chemical Synthesis Program of the Chemistry Division, the research team is exploring fundamentally new reactions of nitriles. The proposal has impact in several areas; the elevation of nitrile chemistry, student training and development, and improving the ability of students' writing. The research falls into three broad areas that will develop new reactions of nitriles for the synthesis of cyclic, carbon-based scaffolds of relevance for the synthesis of pharmaceuticals, agrochemicals, and new materials. The first third of the proposal focuses on an extremely rapid synthesis of bicyclic nitriles, the middle third develops counter-intuitive methods of creating new carbon-carbon bonds, and the last section of the proposal develops new routes to reactive nitrile intermediates to control the three dimensional shape of nitrile-substituted scaffolds. The project continues an excellent track record in training students and post-doctoral associates, particularly minorities and women, to provide a stream of bright, highly motivated students for careers in science. The approach features vigorous research training with synergistic mentoring of undergraduate and graduate students and an emphasis on career life balance through group educational events and annual professional development retreats. Improved writing skills are taught through a review writing strategy that transitions undergraduate and graduate students from novice learners to expert practitioners. The approach simultaneously addresses a general writing deficiency in many students while instilling tools to critically evaluate the primary literature. Publishing the strategy in the Journal of Chemical Education should allow others to replicate the strategy with other students.Technical AbstractThis project focuses on a blend of conceptually new bond constructions and new chemical entities, many of which challenge conventional processes. Preliminary results demonstrate the feasibility of preparing chiral decalones in a single synthetic operation, potentially replacing multi-step technology based on the Wieland-Miescher ketone. A highly unusual equilibration is under development which changes the stereochemistry of a quaternary bridgehead center; a process that challenges conventional notions. A counter-intuitive alkylation of metalated nitriles with unactivated alkenes is rapidly assembling tricyclic ketones. A complementary alkene addition uses S-ketenimines as particularly attractive nucleophiles to address two long-standing challenges: rapid access to stable ketenimine nucleophiles, and nitrile-based alkenylations. The last section of the proposal provides an orthogonal, innovative asymmetric alkylation with metalated nitriles. Collectively, the proposed research exploits the unique reactivity of nitriles consummate with the long-term objective of elevating metalated nitrile alkylations to a level of influence comparable to that of enolate alkylations.